The mechanism of shape-dependent stochastic asymmetric cell division

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Cell-to-cell variability is increasingly appreciated as an integral part of biological systems. In this project, we explored how difference in cell shape affects the determination of future cell behavior. In zebrafish embryos, two kinds of V2 interneurons, V2a and V2b are generated from common V2 progenitor cells. It has been suggested that V2 progenitor cells divide along quasi-random directions and there is no cell fate bias at the time of cell division. However we found that varied shapes of V2 progenitor cells are coupled not only to the cell division orientation but also to the binary cell fate determination in a probabilistic manner. We also established an abstract model for shape-dependent stochastic V2 cells' asymmetric division. We analyzed this model by mathematical simulation in silico, and inspected it by manipulating the zebrafish embryos. Our interdisciplinary approach revealed the design principle for the shape-dependent stochastic asymmetric cell division.